The goal of this Collaborative Mucosal Immunology Program is to provide basic information concerning immunological defense mechanisms in the human male urogenital tract (UGT) that will lead to improved efficacy of anti-HIV vaccines in preventing the sexual transmission of HIV-1. Our research addresses a series of fundamental questions: What is the best approach for monitoring male UGT antibody and cellular immune response? Do male UGT immunological parameters reflect those at other sites that are easier to monitor (ie: blood, saliva)? Is male UGT immunity influenced by HIV infection or antiviral therapy? Do male UG anti-HIV antibody and cellular immune responses correlates with each other? Do seronegative men with a history of high risk sexual behavior have protective cellular or antibody anti-HIV UGT immunity? Is male UGT immunity influenced by HIV vaccination? Do HIV vaccines affect levels of infectious HIV-1 in semen via lacerations in local immunity? Do male UGT anti-HIV anti-HIV antibody and cellular immune responses correlate with each other? Our aims are: 1) To optimize methods for detecting anti-HIV antibody and cellular immune responses in the male UGT and to characterize UGT immunological parameters as a function of HIV disease stage and antiviral therapy, and in relation to immunological parameters measured in blood and other mucosal secretions; 2) To characterize HIV-specific antibody and/or cellular responses (if any) in the UGT of HIV-1 seronegative men that engage in high risk sexual activity with HIV-1 infected partners; 3) To monitor antibody and cellular UGT response following vaccination with HIV vaccines; 4) To use the cholera toxin mucosal vaccine as a model to determine if the male UGT IgA response is a component of the common mucosal immune network, and whether it is affected by HIV-1 infection; 5) To determine if HIV vaccination affects levels of HIV-1 in UGT secretions. This study is designed to provide novel methods for measuring anti-HIV immune defense mechanisms in the male urogenital tract; and fundamental information to promote the development of vaccines that provide safe and effective mucosal protection of uninfected men against HIV-1 infection and reduce the frequency of transmission of HIV from infected men to sexual partners.